Addiction PDF

Sept. 30: drug use and addiction, ch 5 - Drugs hijack normal reward processes in brain - Drugs that directly increase DA in NAc = lots of abuse potential – likely high CPP, higher breakpts Historical models of addiction Addiction as “a choice” Addicts have a defic...

Sept. 30: drug use and addiction, ch 5 - Drugs hijack normal reward processes in brain - Drugs that directly increase DA in NAc = lots of abuse potential – likely high CPP, higher breakpts Historical models of addiction Addiction as “a choice” Addicts have a deficient character and lack willpower, they’ve morally failed. Only solution is religious intervention or jail. Addiction as a disease Addiction (mostly to alc) is incurable, and one drink causes a total loss of control in addicts. By the social reform movement labelling alcoholism as a disease (not sin), they could convince govs and societies to treat these ppl. Intemperance and inebriety addiction Creation of AA in mid 20th century – formalized the idea of addiction as a disease. Was then defined as a disorder in the DSM – initially was labelled a mental disorder before a disease. Theories: - Predisposition – born w it/acquire it before abusing drugs. No cure. Like an allergy (don’t eat it, won’t have a reaction) - Exposure theories – addiction is caused by repeated exposure to a drug, it’s an unintentional consequence. - Recently: gene x env interactions Addiction as physical dependence Withdrawal occurs when drugs stops (do anything to avoid symptoms); compulsive self-admin (addiction). Hypothetical substance “autotoxin” – metabolite of opium that stayed in body after drug was gone, causes withdrawal symptoms which are opposite effects of opium. With the drug in the body – it can antagonize the autotoxin. Withdrawal (sickness) is so bad it causes craving and compulsive use. If a drug causes physical dependence and/or withdrawal, it’s addicting. Physical dependence = cause and symptom of addiction; dependence = state when drug causes physical dependence (and withdrawal) and compulsive use (addiction). Problem w this model: there isn’t a perfect correlation btwn dependence and addiction – can have one but not the other. Ex: pain relievers – physical dependence yes, but no craving or loss of control. Another problem: what comes after can’t be used to explain what becomes before – distress of withdrawal doesn’t explain how someone goes from casual use to habitual that produces physical dependence. Defining addiction – current, DSM-V combines substance abuse and dependence on a continuum; doesn’t use “addiction” bc can mean a state or process SUD: problematic pattern of use, causes sign impairment/distress, w/in 12-month period Severity continuum for number of symptoms: 2-3 (mild), 4-5 (mod), 6+ (severe) A: loss of control over use more taken than intended, can’t cut down or control, craving (wanting), lots of time spend getting, using, recovering, etc. B: social impairment affects all aspects of life, continues to use despite neg consequences, no activities. C: risky use in the face of physical danger (DUI for ex), in the face of neg physiological (fights), psychological consequences. D: pharmacologic dependence tolerance (same amount = less effect, need more to get same); withdrawal (symptoms depend on drug or taking substance to alleviate symptoms). Treatments: targeting NT systems (5-HT, DA, NE, opioids, GABA, Glu), major depression meds (SSRIs, etc.), mood stabilizers and GABA enhancing/Glu suppressing drugs, naltrexone Drug classes: alc is highest for other and self-harm, heroin and cocaine just below - Alcohol - Caffeine - Cannabis - Hallucinogens – PCP, LSD - Inhalants – laughing gas - Sedatives, hypnotics, anxiolytics – barbs, benzos - Stimulants – amphetamine, cocaine - Tobacco - Other Initially, researchers thought it was uniquely human, but they eventually experimented on animals. Their experiments failed for 3 reasons: CTA – animals didn’t like the taste of drugs Slow absorption – there was a delayed reward in the mesolimbic system, so animals didn’t make the association btwn drug and good feeling. taking the drug wasn’t synonymous with getting relief from withdrawal sickness (dependence); even during withdrawal, animals didn’t take the drug. Then, new tech was dev that was IV injections, so it went quickly to brain and animals can pair drug and effects together. Drug self-admin many species similarities for drug class and SA patterns (THC, anabolic steroids, both press button for alc erratically and both experience withdrawal) Aversion - CTA – consumes, vomits/neg feelings = won’t consume again w THC, when they take it, they pass out, don’t want to take it (no SA) - CPA – spends least time in drug-paired chamber, initial THC experiments showed this (concentration dependence – low: CPP, high: CPA) - Neg reinf – animals press lever to stop drug infusion bc they’re aversive – LSD, chlorpromazine, imipramine (antidepressant) Drugs as reinforcers - Stems from SA studies and dependence model (was assumed that physical dependence was needed for SA) - Animals were made physically dependent on morphine then given a chance to press lever for morphine animals learned to respond; but the drug was acting like a positive reinforcer like food/water, not a neg reinforcer where the animal was escaping withdrawal - Assumption – drugs are initially SA bc they act as positive reinfs (positive reinforcement model) - … SA is governed by same mechanism as all other positive reinforcers - BUT: positive reinforcement does not equal pleasure (euphoria) Experiment: cocaine infused into vein results in reliable lever pressing for drug; no lever pressing on nondrug level. When they switched the drug lever, the animal followed and drug-paired lever pressing stops if cocaine becomes noncontingent. SO: lever pressing is specific to the drug-paired lever. … cocaine is a positive reinforcer; drugs are a positive reinforcer. Problems w positive reinforcement model paradox – the consequences of some drugs can be painful enough to stop using them, but many positive reinforcers have negative effects and positive ones. Positive reinforcers are still powerful because they provide immediate rewards. circularity – drug is a positive reinf bc it’s reinforcing the behaviour which it’s contingent upon – can’t explain drug use by saying that a drug is a positive reinf (what initially causes drug use) Changing reinforcement value (abuse potential) - Dose – larger doses are generally more reinforcing - Genetic diffs for some strains of lab rats/mice, they differ in alc consumption/diff prefs for cocaine, etc. - Relief of unpleasant symptoms – might enhance reinforcing value in ppl w the disorder  Ex: alc is used to relieve traumatic/depressive symptoms - Task demands – decision to use a drug depends on the situational demands – ex: not drinking alc bc you’ll be driving - Stress – stress enhances acquisition of SA and increases reinf value (higher rate of responding and higher breakpt) it sensitizes brain mechanisms responsible for the reinf value = higher predisposition for abuse - Deprivations – being deprived of a necessity = will use more drug (hunger and thirst stimulate SA maybe due to stress effect mentioned above) - Previous experience w drugs – either other drug or same (higher reinf ability, sensitization) - Withdrawal – rate of SA of morphine is higher if animal isn’t able to SA for a period of time and if they’re experiencing withdrawal (bc physical dependence = higher breakpt) - Extended access – if animal were given continuous access, they would exceed daily dose, and animal would often die from overdose/side effects - Priming/reinstatement – reestablishment of operant responding of reinf after period where responding has been extinguished – by a noncontingent presentation of reinf (can occur for natural reinforcing stimuli and drugs) - Conditioned reinf – CPP and second-order schedules 2nd-order: admin is preceded/accompanied by a stimulus – stimulus becomes conditioned to cause the response drug + stimulus = sensitization relapse – conditioned stimuli can cause a response w/o the drug Liking and wanting – mediated by diff pathways, liking = tolerance, wanting = sensitization Hedonia (pleasure) hypothesis of dopamine function: the reward value of the reinf stimuli is derived from the pleasure it produces; pleasure reinforces behaviour. pleasure = subjective state that accompanies activation of mesolimbic DA pathway BUT: Parkinson’s patients (deficient in DA) don’t report feeling less pleasure for some activities and increasing DA in the NAc of their brains doesn’t increase pleasure/liking – DA isn’t the only pleasure NT. SIM: if we remove the medial forebrain bundle DA projections or give DA antagonists, pleasure/liking doesn’t decrease. Hedonic hotspots (mediate pleasure) in NAc and ventral part of pallidum (BG) activating them = liking; damage to them = disliking Wanting: directing behaviour towards a goal through incentive salience (some stimuli are naturally incentive salient); become wanted/motivational depending on our physiological state which is determined by the interaction btwn internal and external factors. - NAc is responsible for turning a neutral stim into one we want  - DA is directly involved here – if we block DAR or destroy DA axon terminals, it reduces motivation and goal-directed behaviour to get reward AMPH (increases DA) doesn’t increase liking, but it does increase wanting (more lever pressing) - Park pts get DA agonists – higher risk of dev compulsive behaviours - Affective neuroscience – examining rodents and their feelings to understand our own - Seven emotional systems (in humans and animals): play, fear, rage, lust, seeking, care, panic/grief (correspond to diff emotions and diff NTs) - Liking – eCBs, opioids, pleasure/euphoria; play - Wanting – DA, positive reinf; seeking/reward Motivation and reinforcement Mesolimbic DA pathway – reward pathway, NAc to VTA Activation – VTA and NAc VTA stimulates NAc by releasing DA at its synapses (VTA axons connect to NAc) cells in NAc send axons to VTA and release an opioid-like peptide NT NAc also send axons to BG which connects w cortex (motor loop) NAc output normally inhibits motor system, but when DA is released, it inhibits this inhibitory process (same as sitmulating the motor system) can be activated by a homeostatic imbalance, not just sensory info – will cause same process: stimulating motor system and increasing activity role of DA (activation/sensorimotor DA function hypothesis) – it causes general arousal, physical effort and motor activity Guidance – learning and memory system W/o previous experience/biological significance, an organism will move around and in doing so, will increase the chance of finding food. When they do find food, they’ll pay attention to the cues (i.e., the cues have incentive value) around it to remember them later. largely activated by environmental sensory cues (input to thal, filter to cortex, then to amygdala and hippo which links cues to the stimulus) consider the salience of the cue – how important is the stimulus for survival (more = more salience, feeds back into NAc and VTA) Reward-learning hypothesis of DA function Sensory info is processed by thalamus/cortex, sent to amygdala and hippo which hold info ab previous stimuli, past actions, outcomes using these memories, an organism determines if the stimuli are bio sign  YES: behaviour is activated and directed so organism acts in ways that have restored homeostatic imbalances in past Role of DA it isn’t involved directly in the formation of OC and CC associations It’s not directly needed to acquire stimulus-reward associations (ppl w no DA can still learn these) it’s an indirect action on learning bc it enhances attention, motivation, rehearsal and mem consolidation it’s v involved in prediction – seeing the same cues that indicated food before = you predict you’ll find food *DA is activated by the prediction of finding reward, not actually finding it Drugs and mesolimbic pathway they activate it either via NAc stimulation or inhibition of inhibitory output of motor loop drug-related cues also release DA – even more than natural reinforcers in some cases this doesn’t directly cause euphoria, it’s the fact that they’re gaining incentive salience and being embedded in motivational system natural reinforcers have a natural satiation mechanism to stop (i.e., they lose their incentive value), drugs don’t drug get into brain v soon after administered at high concentration = more immediate reward than natural reinforcers Modern models of addiction Incentive sensitization theory it explains a drug craving as a pathological wanting: when incentive salience of cues comes into conscious awareness. sensitization of incentive motivation = cues associated w drug become more noticeable and desirable (bc of attentional bias mediated by DA) – esp when it’s repeatedly presented the sens can last into recovery and cause relapse the attentional bias is shown in current and former addicts a craving is the manifestation of incentive salience towards drug-associated stim ML DA pathway becomes permanently sensitized: - Stronger Glu input onto DA neurons in VTA then excites NAcc - Synaptic adaptation – constantly stimulating the system until learning occurs and it changes - … we see adaptations of learning and motivational circuitry and sensitization to ML, attention to drug-assoc stimuli is increased  - … subjective conseq of activation of this = wanting - … subjective experience of the sensitized system is craving - How an addiction dev: the more a drug is used, the more control it has over motiv circuit, more effective if becomes at reinf, until it can control a lot of behave Hedonic hypothesis – also based on opponent process theory - Brain reward systems (A process) in equilibrium w brain anti-reward systems (B process) B process: when certain emotional states are activated, CNS mechanisms modulate then to reduce their intensity These systems become dysfunctional and dysregulated over time w repeated admin of a drug – their activity doesn’t return to normal, they become extra sensitized (more B process) Dysphoria – can be thought of as a psychological withdrawal syndrome that can only be relieved by taking the drug, at higher doses (= psychological dependence) Tolerance to pleasant A process – this is the high that’s v correlated w the intensity, quality, duration of reinforcer (drug experience) - Three stages - Binge/intoxication – loss of control (A process) - Withdrawal – increase in reward threshold for brain stimulation = loss of reward sensitivity (B process) - Preoccupation/anticipation – craving, relapse (the dark side of addiction) PFC is hypofunctional now – no inhibition of behaviours that promote drug activity - Allostasis – ability to adapt to new set pts based on changes in the env W time, you have to take larger doses to achieve the same level of euphoria during the initial dose LT: repeated drug use causes dysregulation of reward mechanisms and more activity of antireward systems … withdrawal can last for a long time, relapse can occur even after withdrawal symptoms have disappeared - Hedonic dysregulation – new set pts are established, lowering of mood set pt - New mood set pts – A process gets smaller and B gets lrger over time - Drug becomes the only effective reinforcer – no longer able to be reinforced by natural reinforcers Volkow’s brain disease model – written notes - Resembles much current research – gradual exposure leads to addiction in vulnerable ppl - Vulnerable ppl – ppl w genetic vulnerabilities, in childhood env (psych), etc. - Drug craving becomes stronger the longer you’re going through withdrawal Why use drugs  - Initial/causal use: curiosity, experimentation, peer pressure, pain relief - 15% of casual users dev addiction/substance use disorder (SUD) - Repeated use: pain relief (phys of psych), fills a need (maybe unconscious), fills a void, trauma relief - Can cause SUD; why is SUD sustained – habit, compulsion, behave modification, want to avoid withdrawal symptoms - Brain has changed so much that now all of your behaviours are directed towards drug taking Stress, DA, drugs - Stress and pain cause DA release (bc of internal states) - Stress hormones (released by HPA axis) cause NAc to release DA - Stress hormones are reinforcers - Stress can intensify reinf value of a drug (when stress and drug happen tog) – bc acting on same pathway - Causes LT changes in mesolimbic system (sensitization) - In stressed pregnant rats, their offspring are more sensitive to AMPH self-admin - Pre-existing sensitization in mesolimbic pathway Treatment - Goals is to regain control - Should: be holistic (consider co-morbidity) and very individualized - Detox and medically managed withdrawal – just body detox, no mental health services - Outpatient programs – detox and mental health services - Residential treatment – ST or LT - Stay somewhere else, group therapy, detox, etc. - ST – 3-6 weeks hospital stay, extended outpatient therapy, groups like AA - LT: 6-12 months, focus is resocialization - Behave: - CBT – anticipating problems and promoting good coping strategies - Motivation incentives (reward for drug-free sample) – OC - MET – teaching coping strategies - 12-step facilitation therapy – AA for ex: acceptance, surrender, active involvement - Behave couples’ therapy - Treatment for ados – fam therapy, multisystemic - Pharma - Reducing withdrawal – substitute drug for smtg else: nicotine patch, methadone, benzos, etc Doesn’t cure addiction, but helps alleviate withdrawal - Reducing reward, craving, relapse – full agonists, partial ones, antagonists